Hydrogen fuel quality is important for the successful commercialization of PEM (proton exchange membrane) fuel cell vehicles (FCVs) because impurities can adversely affect the normal operation of FCVs both immediately and during their lifetime operation. Among the impurities specified in H2 quality standards, CO (carbon monoxide) is known to have one of the greatest impacts on fuel cells because of the immediate decrease in performance at low concentrations. CO impurity levels of only 0.2 ppm, as specified in the H2 quality standards, were found in H2 refueling stations with adverse impacts to PEM fuel cell operation. In this study CO impurity testing was conducted on single cells based on an extensive design of experiments (DOE) that was performed using several MEAs with two levels of anode platinum loading (0.05 mgPt/cm2 and 0.1 mgPt/cm2) and two different materials for platinum carbon support (Highly Graphitized Carbon and High Surface Area Carbon). Contamination testing for each MEA design configuration was performed at four different CO impurity levels (0.1 ppm, 0.2 ppm, 0.3 ppm, and 0.4 ppm) and three current densities (0.1 A/cm2, 1.0 A/cm2, and 1.7 A/cm2) at each impurity level. The results indicate that the most significant factor to improve MEA tolerance to CO contamination was the choice of carbon support. The use of high surface area carbon had an even greater impact than the use of higher Pt loading, which suggests paths toward addressing CO contamination that avoid higher catalyst cost.